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Should Patients with VTE Be Tested for Thrombophilia?

Am Fam Physician. 2004 Mar 15;69(6):1537-1540.

The risk of recurrent venous thromboembolism (VTE) after cessation of anticoagulant therapy is estimated to be around 12 to 18 percent after two years. Although the risk can be reduced with anticoagulant therapy, the risks of the latter therapy and the likelihood of recurrent thrombosis cannot easily be predicted for individual patients. Heritable thrombophilic factors are believed to be important in recurrent thromboembolism in at least one third of patients, but the role of testing remains unclear. Baglin and colleagues studied the risk of recurrence in 570 patients with VTE, paying special attention to the role of testing for heritable thrombophilic conditions.

The authors studied all patients receiving anticoagulant therapy at an English regional center following a first episode of VTE. Patients with malignant disease or antiphospholipid activity were excluded from the study, as were patients with thromboses of the mesenteric or cerebral veins, because these could indicate a different process than VTE. Patients were categorized into four groups based on clinical risk factors. Patients with recent surgery were classified as group A, pregnancy-associated cases constituted group B, patients with no risk factors were classified as group C, and those with nonsurgical risk factors (such as immobilization, recent travel, estrogen therapy) were placed in group D. All patients were offered thrombophilia testing (including antithrombin, protein C or S, factor V Leiden, lupus anticoagulant, and cardiolipin), and 85 percent agreed to be tested. Patients were monitored for episodes of recurrent VTE and followed-up at six months, and at one and two years after discontinuing anticoagulation.

Of the 570 patients monitored, 86 were in group A, 12 in group B, 193 in group C, and 279 in group D. The median age was 67 (range, 19 to 100 years), and 44 percent were men. Pulmonary embolism was the initial event in 165 study participants (29 percent). Patients were treated with anticoagulation for a mean duration of 24 to 28 weeks. During follow-up, 26 patients died of non-VTE related causes. The cumulative recurrence rate of VTE at two years was 11 percent. No recurrent cases occurred in groups A or B, but the cumulative recurrence rate was 19.4 percent in group C (no risk factors) and 8.8 percent in group D. The recurrence rate of VTE was no higher in the 130 patients with evidence of a heritable thrombophilic defect than in the 359 patients without thrombophilia. This result was not altered by excluding the patients from groups A and B or when analyzed independently for the most common defects, such as factor V Leiden.

The authors describe three important conclusions based on this study. First, the risk of recurrence of postoperative VTE is very low. Second, the two-year cumulative recurrence rate after an unprecipitated VTE is approximately 20 percent. Third, testing for heritable thrombophilic defects in patients with VTE does not assist in predicting recurrence. Their findings correlate with those of other recent studies questioning the value of testing for thrombophilia. Such testing is not useful in most patients with VTE but may prove useful in those with a strong family history of thrombosis.